Dynamic Responses in Retinal Vessel Caliber With Flicker Light Stimulation and Risk of Diabetic Retinopathy and Its Progression

We hypothesize that patients with type 1 diabetes (T1D) may have abnormal retinal vascular responses before diabetic retinopathy (DR) is clinically evident. Optical coherence tomography angiography (OCTA) was used to dynamically assess the retinal microvasculature of diabetic patients with no clinically visible retinopathy. METHODS. Controlled nonrandomized interventional study. The studied population included 48 eyes of 24 T1D patients and 24 demographically similar healthy volunteers. A commercial OCTA device (AngioVue) was used, and two tests were applied: (1) the hypoxia challenge test (HCT) and (2) the handgrip test to induce a vasodilatory or vasoconstrictive response, respectively. The HCT is a standardized test that creates a mild hypoxic environment equivalent to a flight cabin. The handgrip test (i.e., isometric exercise) induces a sympathetic autonomic response. Changes in the parafoveal superficial and deep capillary plexuses in both tests were compared in each group. Systemic cardiovascular responses were also comparatively evaluated. RESULTS. In the control cohort, the vessel density of the median parafoveal superficial and deep plexuses increased during hypoxia (F 1,23 = 15.69, P < 0.001 and F 1,23 = 16.26, P < 0.001, respectively). In the T1D group, this physiological response was not observed in either the superficial or the deep retinal plexuses. Isometric exercise elicited a significant decrease in vessel density in both superficial and deep plexuses in the control group (F 1,23 = 27.37, P < 0.0001 and F 1,23 = 27.90, P < 0.0001, respectively). In the T1D group, this response was noted only in the deep plexus (F 1,23 = 11.04, P < 0.01). CONCLUSIONS. Our work suggests there is an early impairment of the physiological retinal vascular response in patients with T1D without clinical diabetic retinopathy.

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Retinal Vascular Reactivity in Type 1 Diabetes Patients Without Retinopathy Using Optical Coherence Tomography Angiography

Sousa

Leal

Moreira

et al. 2020

“… 13 , 33 – 35 Decreased retinal vasodilation in response to flickering light as assessed using a dynamic vessel analyzer is correlated with severity of DR and is associated with increased risk of DR progression at 1 year in adults with diabetes. 36 , 37 Dark adaptometry studies have demonstrated that patients with DR have slower dark adaptation and elevated sensitivity thresholds. 38 , 39 A recent study found that increasing severity of DR is associated with a significant decrease in OCTA VD ( P < 0.001), as well as prolonged rod intercept ( P < 0.001), a measure of rod function during dark adaptation.…”

Section: Discussionmentioning

confidence: 99%

Acute Hyperglycemia Reverses Neurovascular Coupling During Dark to Light Adaptation in Healthy Subjects on Optical Coherence Tomography Angiography

Kwan

Lee

Schwartz

et al. 2020

To test the hypothesis that hyperglycemia perturbs neurovascular\ coupling and compromises retinal vascular response during transition from dark to light in healthy subjects using optical coherence tomography angiography (OCTA). METHODS. Ten eyes of 10 healthy subjects were tested, first during fasting and then after receiving a 75-g oral glucose solution. In both sessions, OCTA imaging was done in the dark-adapted state and at 50 seconds, 2 minutes, 5 minutes, and 15 minutes of ambient light. Parafoveal vessel density (VD) and adjusted flow index (AFI) were calculated for the superficial capillary plexus (SCP), middle capillary plexus (MCP), and deep capillary plexus (DCP), and vessel length density was calculated for the SCP. These measurements were compared among conditions after adjusting for age, refractive error, and OCTA scan quality. RESULTS. Hyperglycemia leads to a complete reversal of dark/light adaptation trends in VD and AFI in all layers of the inner retina. In the dark, there is significantly decreased VD in the DCP in hyperglycemia. With a transition to light in hyperglycemia, we observed decreased VD in the SCP, increased vessel density in the MCP and DCP, and decreased AFI in all three layers. CONCLUSIONS. Our results show that hyperglycemia significantly disrupts neurovascular coupling in healthy eyes, with potential metabolic deficits affecting photoreceptor oxygen demands during dark adaptation and the inner retina during light exposure. In pathological states, such as diabetic retinopathy, where the vasculature is already attenuated, retinal neurons may be exquisitely vulnerable to intermittent hyperglycemic challenge, which should be the focus of future studies.

“…Retinal blood flow, as in the rest of the brain, is actively regulated in response to neuronal activity 1,2. Impairment of this coupling mechanism in the retina is commonly encountered during microvascular pathologies, such as diabetic retinopathy 3,4. Currently, there are limited studies (and technologies) that explore the human retinal capillary responses during neurovascular coupling, a key to understanding the pathological disruption during disease.…”

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confidence: 99%

Hemodynamic Response of the Three Macular Capillary Plexuses in Dark Adaptation and Flicker Stimulation Using Optical Coherence Tomography Angiography

Nesper

Lee

Fayed

et al. 2019

Citation: Nesper PL, Lee HE, Fayed AE, Schwartz GW, Yu F, Fawzi AA. Hemodynamic response of the three macular capillary plexuses in dark adaptation and flicker stimulation using optical coherence tomography angiography. Invest Ophthalmol Vis Sci. 2019;60:694-703. https://doi.org/ 10.1167/iovs.18-25478 PURPOSE. To assess retinal microvascular reactivity during dark adaptation and the transition to ambient light and after flicker stimulation using optical coherence tomography angiography (OCTA). METHODS.Fifteen eyes of 15 healthy participants were dark adapted for 45 minutes followed by OCTA imaging in the dark-adapted state. After 5 minutes of normal lighting, subjects underwent OCTA imaging. Participants were then subjected to a flashing light-emitting diode (LED) light and repeat OCTA. Parafoveal vessel density and adjusted flow index (AFI) were calculated for superficial (SCP), middle (MCP), and deep capillary plexuses (DCP), and then compared between conditions after adjusting for age, refractive error, and scan quality. SCP vessel length density (VLD) was also evaluated. Between-condition capillary images were aligned and subtracted to identify differences. We then analyzed images from 10 healthy subjects during the transition from dark adaptation to ambient light.RESULTS. SCP vessel density was significantly higher while SCP VLD was significantly lower during ambient light and flicker compared to dark adaptation. There was a significant positive mean value for DCP ''flicker minus dark or light,'' suggesting more visible vessels during flicker due to changes in flow, dilation, or vessel recruitment. We found a significant, transient increase in SCP and decrease in both MCP and DCP vessel density during the transition from dark to light.CONCLUSIONS. We show evidence suggesting constriction of deeper vessels and dilation of large SCP vessels during the transition from dark to light. This contrasts to redistribution of blood flow to deeper layers during dark adaptation and flicker stimulation.